Process for the production of hydrogenated benzo-iso-tetrazoles



Patented July 16, 1935 PROCESS FOR THE PRODUCTION OF HY- DROGENATED BENZO-ISO-TETRAZOLES Emil Wolf, Budapest, Hungary, assignor to the firm Ohinoin Gyogyszer-Es Vegyszeti Termkek Gyara R. T. (Dr. Kereszty & Dr. Wolf),

Ujpest, Hungary No Drawing. Application July 17, 1934, Serial No. 735,632. In Hungary July 24', 1933 2 Claims.

Benzo-iso-tetrazole according to the formula (see R. G. Fargher and R. Furness, Chem. Cen-.

tralblatt, 1915. II. page 413) is hardly soluble at all in water and is therefore of little value for therapeutical purposes. It has been found, that from benzo-iso-tetrazo-le or from the alkyl derivatives (substituted in the carbon) of benzoiso-tetrazole, it is possible to produce, by means of catalytic hydrogenation, hydrogenated tetrazoles, which are more readily soluble in. water and possess valuable therapeutical properties. A preferable method for carrying the catalytic hydrogenation into eiiect is to employ noble-metal catalyzers such as platinum or palladium. Dihydrobenzo-iso-tetrazoles or tetrahydro-benzoiso-tetrazoles will be obtained according to whether hydrogenation is discontinued after one mol of hydrogen has been absorbed, or whether it is continued until the absorption of hydrogen ceases (which will be the case when 2 mols of hydrogen have been absorbed.)

The starting materials can be produced according to known processes (e. g. according to the Fargher and Furness proccess). If, in the Fargher and Furness process, there are employed, instead of pyridyl-hydrazine, pyridyl-hydrazines having alkyl groups substituted in the pyridine nucleus, the corresponding alkyl-benzo-isotetrazoles, will be obtained, which are suitable as starting materials for the process according to the present invention. Thus from 5-methylpyridyl-hydrazine, for instance, there will be obtained methyl-benzo-iso-tetrazole according to the formula the melting point of which is 152 to 153 C.

Examples After the absorption of hydrogen has ceased, the

mixture is filtered, the alcohol is evaporated and the residue distilled in vacuo. of tetramethylene-tetrazole will be obtained, having a melting point of about 115 C.

2. In an atmosphere of hydrogen 120 grams of benzo-iso-tetrazole dissolved or dispersed in alcohol are agitated. with a palladium catalyzer. After one mol of hydrogen has been absorbed, the mixture is filtered, the filtrate is boiled down, and the residue is re-crystallized. About grams of dihydro-benzo-iso-tetrazole will be obtained, having a melting-point of 96 to 98 C.

3. 134 grams of methyl-benzo-iso-tetrazole (melting point 152 to 153 C) are hydrogenized by means of hydrogen, with the aid of a palladium or platinum catalyzer. After the absorption of hydrogen has ceased, the filtrate is boiled down and the residue is re-crystallized. About 100 to grams of tetrahydro-methyl-benzo-iso-tetrazole will be obtained, having a melting point of 92 to 94 C. v

4. 148 grams of dimethyl-benzo-tetrazole (melting point 128 to 129 0.), produced in the known manner from 2.4-dimethyl-a-hydrazinopyridine, suspended in 2 litres of alcohol are reducedby means of hydrogen, with the aid of 5 grams of PdCl2 precipitated on animal charcoal till, (theoretically) 2 mols of hydrogen have been absorbed; after removing the catalyzer and evapin which X, X, X", and X' stand for a member of the group consisting of hydrogen and alkylgroups, in the presence of hydrogenation metal catalyzers of the platinum group.

2. A process for the production of hydrogen- About 90 grams ated benzo-iso-tetrazoles, comprising the hydro- -in which X, X, X"; X stand for a, member genating of benzo-iso-tetrazoles of the general of the group consisting of hydrogen and alkylformula groups-, in the presence of hydrogenation metal catalyzers of the platinum group and discontinum V V, ing the hydrogenation as soon as one mol of hy- V drogen is added to each mol of the starting ma,-

Xo O=N\ terial.

N V EMIL WOLF. 

